Sonia Dollfus

Cognitive patterns in subtypes of schizophrenia

AIM Because of the heterogeneity of schizophrenia, this study researched different cognitive patterns in distinct subtypes of schizophrenic patients. METHODS Thirty-five Diagnostic and Statistical Manual IV (DSM IV) schizophrenic patients and 35 healthy controls were included. Patients were categorized into deficit, disorganized and positive subtypes with the schedule for the deficit syndrome (SDS) and the positive and negative syndrome scale (PANSS). Executive/attentional functions were assessed with the modified card sorting test (MCST), a test of verbal fluency, the trail making test (TMT) and the Stroop color-word test (Stroop test). Episodic memory was explored through the California verbal learning test (CVLT). RESULTS The positive subtype had some executive/attentional (fluency and Stroop tests) and mnesic performances in the normal range, suggesting the preservation of good cognitive skills. In contrast, the deficit and disorganized subtypes had major mnesic and executive/attentional dysfunctions compared to healthy subjects. The deficit subtype compared to the control group performed predominantly worse on the MCST and fluency, whereas the disorganized subtype had the lowest scores on the TMT and the Stroop test. CONCLUSION This study showed distinct cognitive patterns in deficit, disorganized and positive patients in comparison with the controls, suggesting a heterogeneous cognitive dysfunction in schizophrenia.

Links among resting-state default-mode network, salience network, and symptomatology in schizophrenia

Neuroimaging data support the idea that schizophrenia is a brain disorder with altered brain structure and function. New resting-state functional connectivity techniques allow us to highlight synchronization of large-scale networks, such as the default-mode network (DMN) and salience network (SN). A large body of work suggests that disruption of these networks could give rise to specific schizophrenia symptoms. We examined the intra-network connectivity strength and gray matter content (GMC) of DMN and SN in 26 schizophrenia patients using resting-state functional magnetic resonance imaging and voxel-based morphometry. Resting-state data were analyzed with independent component analysis and dual-regression techniques. We reported reduced functional connectivity within both DMN and SN in patients with schizophrenia. Concerning the DMN, patients showed weaker connectivity in a cluster located in the right paracingulate cortex. Moreover, patients showed decreased GMC in this cluster. With regard to the SN, patients showed reduced connectivity in the left and right striatum. Decreased connectivity in the paracingulate cortex was correlated with difficulties in abstract thinking. The connectivity decrease in the left striatum was correlated with delusion and depression scores. Correlation between the connectivity of DMN frontal regions and difficulties in abstract thinking emphasizes the link between negative symptoms and the likely alteration of the frontal medial cortex in schizophrenia. Correlation between the connectivity of SN striatal regions and delusions supports the aberrant salience hypothesis. This work provides new insights into dysfunctional brain organization in schizophrenia and its contribution to specific schizophrenia symptoms.

Atypical hemispheric specialization for language in right-handed schizophrenia patients.

BACKGROUND The literature suggests that schizophrenia could be related to a failure in the setting up of left hemisphere dominance for language. We sought to determine hemispheric specialization for language in schizophrenic patients, using functional magnetic resonance imaging. METHODS Twenty-one right-handed patients with DSM-IV schizophrenia and 21 right-handed control subjects matched by age, gender, and level of education were recruited. Fractional blood oxygen level dependent (BOLD) signal variations in anatomic regions of interest were compared between groups. Functional asymmetry indices (FAIs) were calculated in a region (LANG) resulting from the merging of activated regions showing a Group x Hemisphere interaction. The FAI difference between each patient and their matched control subject was computed. RESULTS We found lower BOLD signal changes in patients as compared with their control subjects in a network comprising areas of the left middle temporal gyrus, the left angular gyrus, and the pars triangularis of the left inferior frontal gyrus, merged to constitute LANG. The intra-pair differences of FAIs in this area showed that 76% of the patients exhibited less leftward functional asymmetry than their matched control subjects, including six patients with a rightward asymmetry. CONCLUSIONS These results demonstrated the existence of an anomaly in left hemisphere specialization for language in schizophrenic subjects.

Correlates of cognitive impairment in first episode schizophrenia: the EUFEST study.

BACKGROUND Profile and correlates of cognitive deficits in first episode (FE) schizophrenia patients are still debated. The present study is aimed to clarify in a large sample of FE patients the extent of impairment in key cognitive domains and its relationships with demographic and clinical variables. METHOD The European First Episode Schizophrenia Trial collected demographic, clinical and neurocognitive baseline data in 498 FE patients with minimal or no prior exposure to antipsychotics. Two-hundred-twenty healthy subjects (HS) were also evaluated. Neurocognitive assessment included the Rey Auditory Verbal Learning Test; Trail Making A and B, Purdue Pegboard and Digit-Symbol Coding. RESULTS Patients performed worse than HS on all tests (effect sizes from -0.88 to -1.73). Correlations with psychopathological dimensions were weak and involved reality distortion and disorganization. The duration of untreated psychosis (DUP) was not associated with cognitive impairment. Subjects living alone had a better neurocognitive performance, while the occupation status did not reveal any association with cognition. CONCLUSIONS A moderate/severe impairment of processing speed, motor dexterity, verbal memory and cognitive flexibility was found in the largest sample of FE patients analyzed so far. The impairment was largely independent from psychopathology and not associated with DUP.

Two-day treatment of auditory hallucinations by high frequency rTMS guided by cerebral imaging: A 6 month follow-up pilot study

BACKGROUND Recently, repetitive Transcranial Magnetic Stimulation (rTMS) has been introduced as an alternative treatment for auditory hallucinations in schizophrenic patients that fail to respond to antipsychotics. Until now, application of rTMS has been at low frequency, and most commonly applied to the left temporoparietal cortex. This 6-month follow-up pilot study was performed to demonstrate the efficacy of high frequency rTMS guided by anatomical and functional Magnetic Resonance Imaging (MRI). METHODS Eleven patients with schizophrenia (DSM-IV) were treated with high frequency (20 Hz) rTMS delivered over 2 days; they were then followed for 6 months. The target area was identified by fMRI as the highest activation cluster along the posterior part of the left superior temporal sulcus from the BOLD signal of each subject during a language task. RESULTS A significant reduction in global severity and frequency of auditory hallucinations between baseline and post-treatment day 12 was observed. Auditory hallucinations were entirely relieved at 6-month follow-up in 2 patients. The treatment was well tolerated in all patients. CONCLUSIONS This is the first study reporting successful treatment of auditory hallucinations with 20 Hz rTMS. The efficacy at short term, the strength of the clinical response, the persistence of therapeutic effect over a 6-month follow-up, the safety profile, and the short duration of treatment present a considerable therapeutic gain compared to low frequency rTMS.

Executive/attentional cognitive functions in schizophrenic patients and their parents: a preliminary study.

The aim of this study was to determine whether executive/attentional cognitive performances could be considered as markers of vulnerability to schizophrenia. The Stroop Color Word and fluency tests were significantly impaired in schizophrenic patients and their parents compared to controls matched on age and sex while performances on Nelsons Modified Card Sorting Test and the Trail Making Test did not differ. The impairments on the Stroop and fluency could be considered as endophenotypic markers of schizophrenia.

P50 inhibitory gating deficit is correlated with the negative symptomatology of schizophrenia

Abnormal sensory gating in schizophrenia has frequently been reported. The strength of central inhibitory pathways was measured using the P50 component of the auditory evoked potential in a conditioning-testing paradigm. The relationships between a relative decrease in P50 amplitude to repeated auditory stimuli and clinical symptoms remain controversial. Using the Positive and Negative Syndrome Scale, we studied the P50 auditory conditioning-testing paradigm in 81 schizophrenic subjects, categorized into subgroups with and without prominent negative symptoms, in comparison with 88 control subjects. We found increased ratios of testing stimuli to conditioning stimuli in both schizophrenic subgroups relative to findings in the control group. In addition, we found significantly increased mean latencies of the P50 responses to conditioning (C) and testing (T) stimuli and significantly increased T/C ratios in the subgroup with negative symptoms compared with the subgroup with non-negative symptoms.

Association of DNA polymorphism in the first intron of the tyrosine hydroxylase gene with disturbances of the catecholaminergic system in schizophrenia

We examined whether there are clinical or biological differences in chronic schizophrenic patients sharing a rare variant allele (a perfect ten tetranucleotide repeats allele of the human TH01 microsatellite) in the tyrosine hydroxylase (TH) gene. For that purpose, clinical parameters (PANSS subscores) and plasma measurements (homovanillic acid and 3-methoxy-4-hydroxy-phenylglycol (MHPG)) were analyzed in five schizophrenic patients sharing the rare allele and 19 schizophrenic patients who did not possess this allele. The mean concentration of plasma HVA and plasma MHPG were significantly lower in the group of schizophrenic patients sharing the rare allele. No other group differences were observed between both groups. These results suggest that this TH gene polymorphism may be associated with disturbances of the catecholaminergic pathway.

Genetic study of dopamine D1, D2, and D4 receptors in schizophrenia

The goal of this study was to define precisely the involvement of the dopamine D1, D2, and D4 receptor genes in the etiology of schizophrenia. A linkage analysis using the lod score method was performed in 37 families originating from France (n = 14) and from the Island of La Réunion in the Indian Ocean (n = 23). No evidence of linkage between schizophrenia and genetic markers located at these loci was found. A simulation study was carried out to gauge the significance of these results. The conclusions of a nonparametric linkage test (i.e., the affected pedigree member method) were equally negative. For each genetic marker, an allelic association with the disease was also sought: 80 unrelated patients and 80 healthy control subjects were tested, and no significant association was found. These results, which are in agreement with those obtained by other groups, do not support the involvement of the dopamine D1, D2, and D4 receptor genes in the pathogenesis of schizophrenia.

Plasma 3-Methoxy-4-Hydroxyphenylglycol and Homovanillic Acid Measurements in Deficit and Nondeficit Forms of Schizophrenia

BACKGROUND Discrepancies in the biochemical research on negative symptoms in schizophrenia may be ascribed to the lack of differentiation into primary and secondary negative symptoms. We have used Carpenters criteria to define the deficit syndrome of schizophrenia as the presence of enduring and primary negative symptoms and measured catecholaminergic parameters in deficit as compared with nondeficit schizophrenics. METHODS We have investigated plasma homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG) concentrations in 34 DSM-III-R neuroleptic-treated schizophrenic patients who were classified into deficit (n = 14) and nondeficit (n = 20) forms of schizophrenia. All these patients were in a stable clinical and therapeutic status for the preceding 12 months. RESULTS The 14 deficit schizophrenic patients had lower plasma levels of pHVA and higher plasma concentrations of pMHPG from 9 AM to 12 AM as compared with the 20 nondeficit schizophrenic patients. The two groups did not differ on any demographic, therapeutic, or clinical variable considered. CONCLUSIONS Our data are consistent with the postulated distinct pathophysiological basis for the deficit syndrome of schizophrenia and suggest that opposite alterations in the pHVA or pMHPG levels may reflect specific changes in noradrenergic and dopaminergic functions in these deficit patients.